TY  - JOUR
AU  - Haas, Alexander
AU  - Wenz, Friederike
AU  - Hattemer, Janina
AU  - Wesslowski, Janine
AU  - Davidson, Gary
AU  - Voloshanenko, Oksana
AU  - Boutros, Michael
AU  - Acebron, Sergio P
AU  - Bastians, Holger
TI  - Wnt10b signaling regulates replication stress-induced chromosomal instability in human cancer.
JO  - Life science alliance
VL  - 8
IS  - 11
SN  - 2575-1077
CY  - Heidelberg
PB  - EMBO Press
M1  - DKFZ-2025-01753
SP  - e202503295
PY  - 2025
AB  - Wnt signaling pathways are involved in various developmental and tissue maintenance functions, whereas deregulated Wnt signaling is closely linked to human cancer. Recent work revealed that loss of Wnt signaling impairs mitosis and causes abnormal microtubule growth at the mitotic spindle resulting in chromosome missegregation and aneuploidy, both of which are hallmarks of cancer cells exhibiting chromosomal instability (CIN). Here, we show that upon DNA replication stress, a condition typically associated with CIN, Wnt10b acts to prevent increased microtubule dynamics from the S phase until mitosis, thereby ensuring faithful chromosome segregation. Interestingly, replication stress-induced chromosomal breaks are also efficiently suppressed by Wnt10b. Thus, our results show that Wnt10b signaling regulates replication stress-induced chromosome missegregation and breakage, and hence is a determinant for broad genome instability in cancer cells.
KW  - Humans
KW  - Chromosomal Instability: genetics
KW  - DNA Replication: genetics
KW  - Neoplasms: genetics
KW  - Neoplasms: metabolism
KW  - Wnt Proteins: metabolism
KW  - Wnt Proteins: genetics
KW  - Mitosis: genetics
KW  - Cell Line, Tumor
KW  - Chromosome Segregation: genetics
KW  - Wnt Signaling Pathway: genetics
KW  - Microtubules: metabolism
KW  - Genomic Instability
KW  - Signal Transduction
KW  - Proto-Oncogene Proteins
KW  - Wnt Proteins (NLM Chemicals)
KW  - WNT10B protein, human (NLM Chemicals)
KW  - Proto-Oncogene Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40846632
DO  - DOI:10.26508/lsa.202503295
UR  - https://inrepo02.dkfz.de/record/304085
ER  -